Kidney Transplant Rejection
Conditions
Keywords
subclinical, graft rejection, AMR (antibody-mediated rejection), AMBR (acute antibody-mediated rejection), DSA (donor specific antibodies)
Brief summary
This is a pilot study to determine if extended release Envarsus at an optimal level is just as effective as more invasive standard therapies for subclinical (mild) AMR (antibody mediated rejection) in kidney transplant patients. Subjects will be randomized to either conversion to Envarsus XR (extended release); or, to a standard of care regimen of plasma exchange/IVIG (intravenous immunoglobulin)/rituximab treatments.
Detailed description
There is currently minimal data to guide treatment of mild graft damage in kidney transplant patients. Some of the current therapies used often come with dangerous complications (infections, malignancies, etc.). This is a pilot study to determine if extended release Envarsus at an optimal level is just as effective as more invasive standard therapies for subclinical (mild) AMR (antibody mediated rejection) in kidney transplant patients. The subjects will be randomized to either conversion from their current tacrolimus regimen to Envarsus XR (a once a day, extended release version of tacrolimus); or, to a regimen of 5 plasma exchanges/IVIG (intravenous immunoglobulin) treatments and one treatment with rituximab. Subjects who are within their first year of transplant will visit their doctor monthly for regular tests and checks and then will have a kidney biopsy at 6 months. Subjects who had their transplant over a year prior will see the doctor for tests and checks at 1, 3 and 5 months and then will have a biopsy of the kidney at month 6.
Interventions
Switching from current version of tacrolimus to the extended release, once a day version (Envarsus) and titrating dose to achieve an optimal trough level. Goal trough tac level \> 8 ng/ml, MPA at 720 mg bid unless medically contraindicated, prednisone at current dose (5mg) or continue taper to 5mg per center standard of care protocol.
OTHERPlasma Exchange and IVIG (Intravenous Immunoglobulin )
Plasma exchange x 5 treatments, each followed by IVIG 200 mg/kg except last dose of 1 gm/kg. Rituximab 375 mg/m2 following final plasma exchange treatment.
Sponsors
Veloxis Pharmaceuticals
University of Colorado, Denver
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Only patients meeting histologic criteria for AMR by Banff 2013 criteria will be randomized (ptc + g + c4d ≥ 2). Subjects will be randomized to either undergo optimization (conversion to Envarsus with goal trough tacrolimus level \> 8 ng/ml, mycophenolic acid at 720 mg, prednisone at current dose (5mg) or continue taper to 5mg per center standard of care protocol of or treatment.); or, to treat clinical AMR (antibody mediated rejection) with plasma exchange x 5 treatments, each followed by IVIG (intravenous immunoglobulin) 200 mg/kg except last dose of 1 gm/kg. Rituximab 375 mg/m2 following final plasma exchange treatment.
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
* Adult (18+ years) recipients of kidney or kidney/pancreas transplants * Willing to sign an IRB (institutional review board)-approved consent and to comply with study requirements * DSA (donor specific antibodies) detected by SAB (single antigen beads) screening with MFI ≥ 2000 * Graft biopsy performed within prior 30 days * Stable renal function defined by serum creatinine increase ≤ 30% over prior 6 months * Subacute antibody-mediated rejection on biopsy defined by ptc + g + C4d ≥ 2 by Banff 2013 criteria
Exclusion criteria
* Kidney/liver or kidney/heart recipient * Unwilling/unable to undergo screening biopsy * HIV (human immunodeficiency virus), HCV (hepatitis-C virus), or HBsAg (hepatitis-B surface antigen) positive * Active/untreated infection * Acute cellular rejection with Banff grade 1b, 2a, 2b on initial biopsy requiring rATG (rabbit anti-thymocyte globulin) therapy * Pregnant or nursing females
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Acute Inflammatory Histologic Parameters | Baseline and 6 months | Any increase or reduction in ptc+g+C4d score by Banff 2013 criteria) from baseline (pre-treatment) to 6 month (post-treatment initiation). Analysis will comprise exact chi-squared tests for comparison of binomial proportions of histological response between the two treatment groups. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Donor-Specific Antibody (DSA) Mean Fluorescence Intensity (MFI) Level | 6 and 12 months | Comparison of these levels and any changes of levels/rates using two-sided two-sample t-tests. |
| Change in serum creatinine | 6 and 12 months | Comparison of these levels and any changes of levels/rates using two-sided two-sample t-tests. |
| Change in MDRD GFR (Modification of Diet in Renal Disease Glomerular Filtration Rate) | 6 and 12 months | Comparison of these levels and any changes of levels/rates using two-sided two-sample t-tests. |
| Patient Survival | 6 and 12 months | Total and death-censored calculated using Kaplan-Meier methods and compared using logrank tests. |
| Evaluation of Adverse Events | 6 and 12 months | All potential adverse events will be captured and recorded by study coordinators during post-treatment standard of care clinic visits, and reviewed by PI. Adverse events will be reported for each group separately and compared using exact chi-squared tests. |
| Graft Survival | 6 and 12 months | Total and death-censored calculated using Kaplan-Meier methods and compared using logrank tests. |
Countries
United States
Outcome results
None listed